Research performed on mice to study plasticity

Alison Barth, an assistant professor of biological sciences and an affiliate of the Center for the Neural Basis of Cognition (CNBC), has been studying mouse whiskers to learn about the brain’s ability to generate new connections between neurons. This ability, called plasticity, is crucial to the repair of brain damage, and it has been of much interest in the field of medical science.

Barth believes that mechanisms of plasticity can provide information about one of the brain’s most fundamental abilities — learning.

Barth, graduate student Brett Benedetti, and colleague Stanislaw Glazewski from Keele University in the United Kingdom recently performed research showing the extent to which plasticity occurs within the whisker systems of mice.

“We were looking for a really strong way to induce plasticity,” Barth said about the reasoning behind the study. “A big question for a long time has been knowing where to look.”

Barth has done a lot of work with mouse whiskers, and she suspected that the right manipulation of them might lead to a big effect. “It was sort of based on a hunch,” Barth joked.

Each one of a mouse’s whiskers is part of a highly sensitive organ. All of the movements, vibrations, and other sensory information detected by these stiff hairs are encoded by neurons in the cortex of the brain. These neurons collectively form the representation of the whisker in the cortex.

When a whisker is removed, the neurons encoding that whisker no longer receive sensory information. Due to this lack of neural response, adjacent whiskers expand their representations, taking over unused neurons and becoming more sensitive to sensory information themselves.

The extent of this “takeover” varies. Barth discovered that if all of the whiskers on one side of the mouse’s face were removed, a large amount of plasticity occurred on the opposite side.

Barth’s results are exciting because they provide a new way to study plasticity on a greater scale than previously available. When studying an effect like plasticity, “we want the changes to be as big as possible so we can see them,” said Barth.

These results are also interesting to scientists because of their implications for patients with brain damage. Many stroke patients lose functionality of appendages or sense organs because the neurons encoding for those organs are wiped out. If other neurons could take over those representations, functionality could be regained.

Maximizing this process of neural compensation is the aim of physical therapy for stroke patients. Appendages that are used more often develop larger representations, becoming more sensitive in their motions and abilities.

Therapists have long known that if a stroke victim loses function of one arm, immobilizing the opposite arm can allow the impaired arm to regain functionality much faster.

Barth’s work, however, is the first time the same effect has been seen for sensory organs like whiskers.

In fact, Barth’s findings could lead to new therapies for people who have lost sensory input due to brain damage. According to Barth, if somebody experiences a stroke that affects his or her ability to see, occluding one eye may help strengthen the affected eye.

Much of Barth’s recent work with brain function has had medical applications. Another paper she recently published focused on the genes involved in plasticity. Barth, former computer science undergraduate Andreas Pfenning, and computational biologist Russel Schwartz identified a number of genes that are likely to be induced during learning.

According to Barth, this identification is “based on their binding site for plasticity-related transcription factors.” Barth calls this sum of genes involved in learning the plasticity transcriptome, and although the list of genes is probably far from complete, this work is a step toward understanding them.

“What’s amazing is that many of the ion channel genes we identified were already being studied in epilepsy and other disorders,” Barth said.

Because plasticity is fundamental to brain function, problems with these genes can cause systemic disorders, like epilepsy or mental retardation. Understanding the plasticity transcriptome could lead to great advances in the treatment of such disorders.

But the scope of Barth’s research is wider than these medical applications.

As an affiliate of the CNBC, Barth works closely with many other faculty members and students interested in cognitive neuroscience. The central aim of the CNBC is to forge links between people who study the brain in computational, human, and animal contexts with the aim of better understanding human cognition.

Barth’s interdisciplinary work is typical of CNBC affiliates. CNBC researchers are faculty from Carnegie Mellon and the University of Pittsburgh from a wide range of departments, including psychology, neuroscience, computer science, statistics, bioengineering, and mathematics.

Carl Olson, acting co-director of the center, said that Barth’s work coincides well with the CNBC’s mission to bring different kinds of research to bear on the questions of human cognition. “A mouse whisker seems a long way removed from what most of us call cognition,” Olson said, “but it is a simple, beautiful system to study a major question: How does experience change the brain?”

“There’s a genetic bridge from mice to humans,” Olson added. “[Finding bridges like that is] what we’re here to do.”